US20040106683A1 - Uses of benzylideneamino guanidines as ligands to the melnocortin receptors - Google Patents
Uses of benzylideneamino guanidines as ligands to the melnocortin receptors Download PDFInfo
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- US20040106683A1 US20040106683A1 US10/472,768 US47276803A US2004106683A1 US 20040106683 A1 US20040106683 A1 US 20040106683A1 US 47276803 A US47276803 A US 47276803A US 2004106683 A1 US2004106683 A1 US 2004106683A1
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- 0 [2*]C1=C([3*])C([4*])=C([5*])C([H])=C1/C=N/N([H])/C(=N/[H])N([H])[H] Chemical compound [2*]C1=C([3*])C([4*])=C([5*])C([H])=C1/C=N/N([H])/C(=N/[H])N([H])[H] 0.000 description 3
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to the use of benzylideneamino guanidines as melanocortin receptor agonists or antagonists.
- the present invention particularly relates to benzylideneamino guanidines which show selectivity to the MC1 and MC4 melanocortin receptors as agonists and/or antagonists.
- a number of large linear and cyclic peptides are known in the art which show high specific binding to melanocortin (MC) receptors.
- the agonistic and/or antagonistic properties of these peptides are also known. See for example “Melanocortin Receptor ligands and methods of using same” by Dooley, Girten and Houghten (WO 99/21571).
- Two patent applications (WO 99/55679 and WO 99/64002) have been published which include small molecules showing activity on the melanocortin receptors.
- the compounds in the present application are structurally different from the previously published melanocortin agonists, and hence the observed effects are unexpected.
- hydroxyguanidines e.g. WO98/23267
- Other compounds known in the art are benzylideneamino guanidines which have shown anti-depressive effects (U.S. Pat. No. 4,060,640).
- Other examples of pharmacologically active guanidines known in the art are described in patent U.S. Pat. No. 3,982,020 and GB1223491.
- Other application areas are also known in the art and are described in patents DE1165013 and U.S. Pat. No. 3,941,825.
- Guanabenz is a compound which is well known in the art as an antihypertensive drug (US Pharmacopeia, 1999, The United States Pharmacopeial Convention, Inc, ISBN 1-889788-03-1). Whilst Guanabenz might appear to be structurally similar to the compounds in the present invention, it shows no affinity to the melanocortin receptors. Therefore it is very surprising that the benzylideneamino guanidine compounds in the present invention show affinity to the melanocortin receptors as agonist and/or antagonists.
- One aspect of the present invention is therefore to provide low molecular weight compounds showing activity on melanocortin receptors and which may be taken up after per oral administration and which may penetrate well through the blood brain barrier.
- R 2 is selected from hydrogen, chloro, bromo or nitro group
- R 3 is selected from a hydrogen or bromo group
- R 4 is selected from a hydrogen or methoxy group
- R 5 is selected from a hydrogen or hydroxy group
- R 4 and R 5 may together be a methylenedioxy group.
- At least one of R 3 , R 4 and R 5 is not a hydrogen.
- R 2 is selected from a chloro, hydrogen, or bromo group.
- the present invention includes the use of the following compounds, inter alia, for modulating melanocortin related systems: No. Name Salt M.p. 1:14 N-(2- HCl 197-201 Bromobenzylideneamino)guanidine 1:15 N-(2-Bromo-5- HCl 223-228 Hydroxybenzylideneamino)guanidine (decomp.) 1:17 N-(4,5-Methylenedioxy-2- AcOH 205-212 nitrobenzylideneamino)guanidine (decomp.) 1:20 N-(2- AcOH 138-143 Chlorobenzylideneamino)guanidine 1:21 N-(3- AcOH 160-161.5 Bromobenzylideneamino)guanidine
- the present invention relates to the use of benzylideneamino guanidines with activity on the melanocortin receptors.
- the compounds of the present invention have been biologically tested in the melanocortin system and have surprisingly been shown to be capable of binding to melanocortin receptors as well as showing activity in functional assays.
- the compounds of the present invention may either be agonists or antagonists of a specific MC-receptor or of a number of MC-receptors, e.g. MC1, MC3, MC4 or/and MC5 receptors.
- the MC-receptors belong to the class of G-protein coupled receptors which are all built from a single polypeptide forming 7 transmembrane domains. Five such receptors types, termed MC1, MC2, MC3, MC4 and MC5, have been described.
- the MC receptor's signalling is mainly mediated via cAMP but also other signal transduction pathways are known. They are distinctly distributed in the body.
- MC-receptors are linked to a variety of physiological actions that are thought to be mediated by distinct subtypes of the MC-receptors. In many cases, however, it is not entirely clear which of the subtypes is responsible for the effect.
- Some of the compounds provided in the present invention can be used for modulating melanocortin related systems and therefore used for the treatment of diseases such as drug abuse, feeding disorders, immunomodulatory action, pain, skin and sexual function/dysfunctions associated with the melanocortin receptors or related systems, e.g. the melanocyte stimulating hormones.
- diseases such as drug abuse, feeding disorders, immunomodulatory action, pain, skin and sexual function/dysfunctions associated with the melanocortin receptors or related systems, e.g. the melanocyte stimulating hormones.
- MSH-peptides may affect many different processes such as motivation, learning, memory, behaviour, inflammation, body temperature, pain perception, blood pressure, heart rate, vascular tone, brain blood flow, nerve growth, placental development, aldosterone synthesis and release, thyroxin release, spemiatogenesis, ovarian weight, prolactin and FSH secretion, uterine bleeding in women, sebum and pheromone secretion, blood glucose levels, intrauterine foetal growth, as well as other events surrounding parturtion (Eberle, A N: The melanotropins: Chemistry, physiology and mechanisms of action.
- Some of the compounds of the invention are useful for inhibiting or stimulating the in vivo formation of second messenger elements such as cAMP. Such inhibition/stimulation may be used in cells or crushed cell systems in vitro, e.g. for analytical or diagnostic purposes.
- the compounds of the invention may be used in radioactive form where they comprise one or more radioactive labels or gamma or positron emitting isotopes, to be used in radioligand binding for the quantification as well as tissue localisation of MC-receptors, for analysis of dissociation/association constants, and for imaging of in vivo binding by the use of scintigraphy, positron emission tomography (PET) or single photon emission computed tomography (SPECT), or for the diagnosis of disease and treatment of any malignancy where the malignant cells contain MC receptors.
- PET positron emission tomography
- SPECT single photon emission computed tomography
- the compounds of the invention can be labelled with any other type of label that allows detection of the respective compound, e.g. fluorescence, biotin, or labels activated by gamma-irradiation, light photons or biochemical processes, or by light or UV-light (the latter in order to obtain a compound useful for covalent labelling of MC receptors by a photoaffinity technique).
- any other type of label that allows detection of the respective compound, e.g. fluorescence, biotin, or labels activated by gamma-irradiation, light photons or biochemical processes, or by light or UV-light (the latter in order to obtain a compound useful for covalent labelling of MC receptors by a photoaffinity technique).
- Some of the compounds of formula (I) or the pharmacologically acceptable salts thereof may also be tagged with a toxic agent (i.e. doxorubicin, ricin, diphtheria toxin or other) and used for targeted delivery to malignant cells bearing MC receptors, or tagged with a compound capable of activating the endogenous immune system for triggering the immune system (for example a compound, monoclonal antibody or other, capable of binding to a T-cell antigen, e.g. CD3 or other) for treatment of malignancies and other MC receptor expressing diseases.
- a toxic agent i.e. doxorubicin, ricin, diphtheria toxin or other
- a compound capable of activating the endogenous immune system for triggering the immune system for example a compound, monoclonal antibody or other, capable of binding to a T-cell antigen, e.g. CD3 or other
- the thus formed hybrid compound will direct cytotoxic cells to the malignant melanom
- Compounds of the invention may be used for the treatment and diagnosis of diseases, disorders and/or pathological conditions in an animal, in particular in man.
- the present invention also relates to a pro-drug which, upon administration to an animal or a human, is converted to a compound of the invention.
- Pro drugs of the compounds of formula (I) and their pharmacologically acceptable salts may be used for the same purposes as described in this specification for the compounds of the invention, as well as is disclosed in the examples given below.
- the compounds of the present invention may be bound covalently or noncovalently to one or several of other molecule(s) of any desired structure(s); the thus formed modified compound or complex may be used for the same purposes as described in this specification for the compounds of the invention as well as is disclosed in the examples given below.
- a radioactively-labelled molecule is covalently bound to a compound of formula (I) or a pharmacologically acceptable salt thereof so as to make a compound of formula (I) or a pharmacologically acceptable salt thereof radioactively labelled.
- the invention also relates to uses of pharmaceutical preparations comprising one or more of the compounds of the invention for various medical and veterinary practices related to melanocyte stimulating hormone receptors.
- the compounds of formula (I) are known in the art and may be prepared by methods such as described in WO 01/25192. For example, by reaction of the appropriate aromatic aldehyde and amino guanidine salt.
- the compounds having the general formula (I) may be prepared by the following general method.
- Test 1 Affinity for the MC1-Receptor
- the binding assay was carried out essentially as described by Lunec et al., Melanoma Res. 1992; 2; 5-12 using I 125 -NDP- ⁇ MSH as ligand.
- Test 2 Affinity for the MC3-Receptors, the MC4-Receptors and the MC5-Receptors
- the affinity of the compounds for the different melanocortin receptors were determined by using either insect cells (Sf9) or COS cells, which were transfected with recombinant human MC3, MC4 or MC5 receptors.
- Sf9 insect cells
- COS cells which were transfected with recombinant human MC3, MC4 or MC5 receptors.
- B16 mouse melanoma cells were used, which endogenously express the (mouse) MC1 receptor.
- the compounds were tested at different concentrations for their ability to displace a 125 I-labelled NDP-MSH from the respective receptor. Incubation was performed in 96-well plates, using 50,000 cells/well (Sf9 or COS cells) up to 200,000 cells/well (mouse melanoma cells).
- test compound or standard (NDP-MSH) was added in an appropriate concentration (generally between 10 ⁇ 4 M and 10 ⁇ 12 M) together with labelled tracer (approx. 50,000 cpm/well) and incubated for 2 hours (at room temperature for Sf9 cells and at +37° C. for COS cells and mouse melanoma cells).
- Sprague-Dawley male rats were used, which were cannulated intracerebroventricularly.
- Stainless steel guide cannulae were placed in the lateral ventricle and fixed in the skull. Animals were acclimatized for a week before the experiments took place. After the experiments were done, the rats were killed and placement of the cannulae were checked.
- Rats were cannulated as described above. They were used without prior starvation, and compounds were administered at 5 pm in a total volume of 5 ⁇ l. Doses of compounds used were in between 0.25 to 50 nmoles. Food intake was measured at 3, 15 and 24 hours after dosing, and body weight was recorded at 24 hours. For comparison, the well-known MC4 receptor agonist, Melanotan II (MTII) was used, at a dose of 1 nmole.
- MMII Melanotan II
- mice Female BALB/c mice (weight 20-22 g) were sensitized by treatment of the shaved abdomen with 30 ⁇ l of 0.5% 2,4-dinitrofluorobenzene (DNFB). After 4 days they were challenged with 10 ⁇ l of 0.3% DNFB to the paw. The unchallenged mice paws served as a control. Twenty-four hours after the last challenge, the differences in paws weight were determined as an indicator of the inflammation (paw edema).
- DNFB 2,4-dinitrofluorobenzene
- mice were treated as the control but were additionally injected i.p. with ⁇ -MSH (0.5 mg/kg) or prednisolone (20 mg/kg) two hours before sensitization (day 0) and the same dose was administered repeatedly after sensitization during four consecutive days. The paw edema inhibition was measured as described above.
- mice were treated as the control but were additionally injected i.p. with various doses (0.05, 0.15 or 0.25, 0.375, 0.5, 0.75 and in later studies also 1.5, 3 and occasionally 6 mg/kg) of each compound two hours before sensitization (day 0) and the same dose was administered repeatedly after sensitization during four consecutive days.
- various doses 0.05, 0.15 or 0.25, 0.375, 0.5, 0.75 and in later studies also 1.5, 3 and occasionally 6 mg/kg
- mice Groups containing at least 10 mice each were used for all experiments.
- Example of a Suitable Tablet Formulation Per tablet Active ingredient, as salt 5 mg Potato starch 90 mg Colloidal Silica 10 mg Talc 20 mg Magnesium stearate 2 mg 5% aqueous solution of gelatine 25 mg Total up to 385 mg
- a solution for parenteral administration by injection can be prepared in an aqueous solution of a water-soluble pharmaceutically acceptable acid addition salt of the active substance preferably in a concentration of 0.1% to about 5% by weight.
- These solutions may also contain stabilising agents and/or buffering agents.
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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GB0108631.3 | 2001-04-05 | ||
GBGB0108631.3A GB0108631D0 (en) | 2001-04-05 | 2001-04-05 | Novel benzylideneamino guanidines and their uses as ligands to the melanocortin receptors |
PCT/GB2002/001589 WO2002080896A1 (en) | 2001-04-05 | 2002-04-05 | Uses of benzylideneamino guanidines as ligands to the melanocortiin receptors |
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US20040106683A1 true US20040106683A1 (en) | 2004-06-03 |
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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US10/472,768 Abandoned US20040106683A1 (en) | 2001-04-05 | 2002-04-05 | Uses of benzylideneamino guanidines as ligands to the melnocortin receptors |
US10/472,767 Abandoned US20040106682A1 (en) | 2001-04-05 | 2002-04-05 | Novel benzylideneamino guanidines and their uses as ligands to the melnocortin receptors |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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US10/472,767 Abandoned US20040106682A1 (en) | 2001-04-05 | 2002-04-05 | Novel benzylideneamino guanidines and their uses as ligands to the melnocortin receptors |
Country Status (11)
Country | Link |
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US (2) | US20040106683A1 (de) |
EP (2) | EP1372625A1 (de) |
JP (2) | JP2004531510A (de) |
KR (2) | KR20030088056A (de) |
BR (2) | BR0208657A (de) |
CA (2) | CA2443099A1 (de) |
GB (1) | GB0108631D0 (de) |
IL (2) | IL158247A0 (de) |
MX (2) | MXPA03008973A (de) |
WO (2) | WO2002081430A2 (de) |
ZA (1) | ZA200307453B (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040106682A1 (en) * | 2001-04-05 | 2004-06-03 | Torbjorn Lundstedt | Novel benzylideneamino guanidines and their uses as ligands to the melnocortin receptors |
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GB0019357D0 (en) | 2000-08-07 | 2000-09-27 | Melacure Therapeutics Ab | Novel phenyl guanidines |
GB0119172D0 (en) * | 2001-08-06 | 2001-09-26 | Melacure Therapeutics Ab | Phenyl pyrrole derivatives |
ATE482238T1 (de) | 2003-01-23 | 2010-10-15 | Kuraray Co | Polyvinylacetal und dessen verwendung |
US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
US20070021433A1 (en) | 2005-06-03 | 2007-01-25 | Jian-Qiang Fan | Pharmacological chaperones for treating obesity |
GB0624987D0 (en) * | 2006-12-14 | 2007-01-24 | Acure Pharma Ab | Novel aminoguanidines as melanocortin receptor ligands |
ES2393885T7 (es) | 2007-06-04 | 2014-01-30 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
EP2045250A1 (de) * | 2007-09-26 | 2009-04-08 | Action Pharma A/S | Ring substituierte Phenylpyrrol-Aminoguandinin-Derivate |
ES2522968T3 (es) | 2008-06-04 | 2014-11-19 | Synergy Pharmaceuticals Inc. | Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
MX2011004258A (es) | 2008-10-22 | 2011-06-01 | Merck Sharp & Dohme | Derivados de bencimidazol ciclicos novedosos utiles como agentes anti-diabeticos. |
CA2741672A1 (en) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
AU2009314200B2 (en) | 2008-11-17 | 2011-11-17 | Merck Sharp & Dohme Corp. | Substituted bicyclic amines for the treatment of diabetes |
US20120220567A1 (en) | 2009-07-23 | 2012-08-30 | Shipps Jr Gerald W | Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
WO2011011506A1 (en) | 2009-07-23 | 2011-01-27 | Schering Corporation | Spirocyclic oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors |
CA2786314A1 (en) | 2010-02-25 | 2011-09-01 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
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WO2011143057A1 (en) | 2010-05-11 | 2011-11-17 | Merck Sharp & Dohme Corp. | Novel prolylcarboxypeptidase inhibitors |
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US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
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CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
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WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
EP3721877A1 (de) * | 2014-07-02 | 2020-10-14 | InFlectis BioScience | Neuartige therapeutische verwendungen von benzylidenguanidinderivaten zur behandlung von proteopathien |
WO2018106518A1 (en) | 2016-12-06 | 2018-06-14 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
US10968232B2 (en) | 2016-12-20 | 2021-04-06 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
US20180230105A1 (en) | 2017-01-13 | 2018-08-16 | Regents Of The University Of Minnesota | Therapeutic compounds |
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-
2001
- 2001-04-05 GB GBGB0108631.3A patent/GB0108631D0/en not_active Ceased
-
2002
- 2002-04-05 EP EP02707025A patent/EP1372625A1/de not_active Withdrawn
- 2002-04-05 US US10/472,768 patent/US20040106683A1/en not_active Abandoned
- 2002-04-05 MX MXPA03008973A patent/MXPA03008973A/es unknown
- 2002-04-05 WO PCT/GB2002/001593 patent/WO2002081430A2/en not_active Application Discontinuation
- 2002-04-05 US US10/472,767 patent/US20040106682A1/en not_active Abandoned
- 2002-04-05 KR KR10-2003-7012903A patent/KR20030088056A/ko not_active Application Discontinuation
- 2002-04-05 WO PCT/GB2002/001589 patent/WO2002080896A1/en not_active Application Discontinuation
- 2002-04-05 BR BR0208657-3A patent/BR0208657A/pt not_active Application Discontinuation
- 2002-04-05 BR BR0208658-1A patent/BR0208658A/pt not_active Application Discontinuation
- 2002-04-05 EP EP02707026A patent/EP1383740A2/de not_active Withdrawn
- 2002-04-05 JP JP2002578935A patent/JP2004531510A/ja not_active Withdrawn
- 2002-04-05 IL IL15824702A patent/IL158247A0/xx unknown
- 2002-04-05 JP JP2002579418A patent/JP2004531516A/ja not_active Withdrawn
- 2002-04-05 MX MXPA03008972A patent/MXPA03008972A/es unknown
- 2002-04-05 CA CA002443099A patent/CA2443099A1/en not_active Abandoned
- 2002-04-05 KR KR10-2003-7012904A patent/KR20030092045A/ko not_active Application Discontinuation
- 2002-04-05 CA CA002443057A patent/CA2443057A1/en not_active Abandoned
- 2002-04-05 IL IL15824802A patent/IL158248A0/xx unknown
-
2003
- 2003-09-25 ZA ZA200307453A patent/ZA200307453B/xx unknown
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US20040106682A1 (en) * | 2001-04-05 | 2004-06-03 | Torbjorn Lundstedt | Novel benzylideneamino guanidines and their uses as ligands to the melnocortin receptors |
Also Published As
Publication number | Publication date |
---|---|
CA2443099A1 (en) | 2002-10-17 |
BR0208657A (pt) | 2004-03-02 |
CA2443057A1 (en) | 2002-10-17 |
ZA200307453B (en) | 2004-09-27 |
JP2004531510A (ja) | 2004-10-14 |
US20040106682A1 (en) | 2004-06-03 |
KR20030092045A (ko) | 2003-12-03 |
WO2002081430A3 (en) | 2003-08-14 |
GB0108631D0 (en) | 2001-05-30 |
WO2002081430A2 (en) | 2002-10-17 |
IL158248A0 (en) | 2004-05-12 |
IL158247A0 (en) | 2004-05-12 |
JP2004531516A (ja) | 2004-10-14 |
EP1372625A1 (de) | 2004-01-02 |
WO2002080896A1 (en) | 2002-10-17 |
BR0208658A (pt) | 2004-03-02 |
EP1383740A2 (de) | 2004-01-28 |
MXPA03008973A (es) | 2004-02-12 |
MXPA03008972A (es) | 2004-02-12 |
KR20030088056A (ko) | 2003-11-15 |
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